Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: Study protocol for a randomized controlled trial

Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life, a substantial number of patients with advanced cancer do not receive psycho-oncological interventions tailored to their individual situation.

S T U D Y P R O T O C O L Open Access

Efficacy of a brief manualized intervention

Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial

Katharina Scheffold1, Rebecca Philipp1, Dorit Engelmann2, Frank Schulz-Kindermann1, Christina Rosenberger1, Karin Oechsle3, Martin Härter1, Karl Wegscheider4, Florian Lordick5, Chris Lo6, Sarah Hales6, Gary Rodin6

and Anja Mehnert2*

Abstract

Background: Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life, a substantial number of patients with advanced cancer do not receive psycho-oncological interventions tailored to their individual situation Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care settings, we aim to examine the efficacy of a brief, manualized individual psychotherapy for patients with advanced cancer: Managing Cancer and Living Meaningfully (CALM) CALM aims to reduce depression and death anxiety, to strengthen communication with health care

providers, and to enhance hope and meaning in life We adapted the intervention for German cancer care settings Methods/Design: We use a single-blinded randomized-controlled trial design with two treatment conditions: intervention group (IG, CALM) and control group (CG) Patients in the CG receive a usual non-manualized

supportive psycho-oncological intervention (SPI) Patients are randomized between the IG and CG and assessed at baseline (t0), after three (t1) and after 6 months (t2) We include patients with a malignant solid tumor who have tumor stages of III or IV (UICC classification) Patients who are included in the study are at least 18 years old, speak German fluently, score greater than or equal to nine on the PHQ-9 or/and greater than or equal to five on the Distress Thermometer It is further necessary that there is no evidence of severe cognitive impairments We measure depression, anxiety, distress, quality of life, demoralization, symptom distress, fatigue as well as spiritual well-being, posttraumatic growth and close relationship experiences using validated questionnaires We hypothesize that patients in the IG will show a significantly lower level of depression 6 months after baseline compared to patients

in the CG We further hypothesize a significant reduction in anxiety and fatigue as well as significant improvements

in psychological and spiritual well-being, meaning and post-traumatic growth in the IG compared to CG 6 months after baseline

Discussion: Our study will contribute important statistical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients

Trial registration: ClinicalTrials.gov NCT02051660

* Correspondence: anja.mehnert@medizin.uni-leipzig.de

2 Department of Medical Psychology and Medical Sociology, Section of

Psychosocial Oncology, University Medical Center Leipzig,

Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany

Full list of author information is available at the end of the article

© 2015 Scheffold et al Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in

Worldwide, eight million people died from cancer in

2010 - an increase of 38 % over the last two decades [1]

Numerous studies have shown high levels of symptom

burden and psychosocial distress associated with

ad-vanced cancer [2–6] Psychological distress can range

from normal adaptive emotions through to higher levels

of severe and clinically significant symptoms that fulfill

the standardized diagnostic criteria for adjustment disorder,

anxiety disorders, or depression [7] Studies demonstrate

a total prevalence for any mental disorder of 32 %

across all tumor settings and stages [8] and prevalence

rates of 30–50 % for all mood disturbances including

adjustment disorders and depression in palliative care

settings [9, 10]

Many patients with advanced disease experience

demoralization, existential and spiritual distress, or loss

of dignity [6, 11, 12], reflecting a loss of hope and a

di-minished sense of meaning [13–16] In addition, patients

and caregivers are confronted with difficult treatment

decisions in palliative care planning

Various types of psycho-oncological interventions are

associated with significant, small-to-medium effects on

emotional distress and quality of life [17] However, the

majority of randomized controlled psycho-oncological

intervention trials for cancer patients were tested in

curative settings and predominantly included women

[17] Manualized meaning-based interventions to treat the

psychosocial and existential distress in cancer patients

have been developed and empirically tested [18–21]

Nevertheless, the number of evaluated and effective

meaning-based psychotherapeutic interventions for

ad-vanced cancer patients is still small

Psychotherapeutic interventions for individuals with

advanced disease must be short-term and flexible

enough to adjust to rapidly changing needs and clinical

circumstances Only two of eight interventions described

in a review of meaning-based interventions for physically

ill patients by Lemay and Wilson [18] are short-term

[22, 23] Although patients with advanced disease often

find it difficult to attend sessions at a fixed time in a

group setting, many existing psychotherapies for cancer

patients are conceptualized as group therapies [24]

Group settings in palliative care can cause additional distress if patients are faced with the death of another group member Moreover, very few interventions focus

on addressing medical treatment situations in collabor-ation with the medical care team [25]

Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life [17], the majority

of patients with advanced cancer do not receive psycho-therapeutic interventions tailored to their individual situation To address this deficit in palliative care, Rodin and colleagues developed a brief, manualized individual psychotherapy for patients with advanced cancer: Managing Cancer and Living Meaningfully (CALM) [20, 26] CALM aims to reduce depression and death anxiety, to strengthen communication with health care providers, and to enhance hope and meaning in life Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care set-tings, we aim to examine the efficacy of CALM adapted for German cancer care settings compared to a non-manualized supportive psycho-oncological intervention (SPI) using a randomized control trial design (RCT)

Methods Study design

In this bicenter German CALM study we use a single-blinded randomized-controlled trial design with two treatment conditions: intervention group (IG) and con-trol group (CG) Patients are assessed during screening,

at baseline (t0), after three (t1) and after 6 months (t2) Participants are randomized between the intervention and the control arm Patients in the intervention group re-ceive CALM, whereas patients in the control group rere-ceive

a usual non-manualized supportive psycho-oncological intervention (SPI) to the same extent (frequency and dur-ation) as CALM (Fig 1)

Our CALM RCT is conducted in two University Medical Centers: (a) the Outpatient Clinic for Psycho-oncology at the Department of Medical Psychology, University Medical Center Hamburg-Eppendorf and (b) the Outpatient Cancer Counseling Center at the Section

of Psychosocial Oncology, Department of Medical

Fig 1 Study (RCT) design (German CALM RTC)

Psychology and Medical Sociology, University Medical

Center Leipzig Our CALM RCT received ethics

com-mittee approval at both participating centers (Hamburg

reference number: PV4435; Leipzig reference number:

143–14–14042014)

Pilot phase

We conducted a pilot study prior to initiating the CALM

RCT at the Outpatient Clinic for Psycho-oncology,

Department of Medical Psychology, University Medical

Center Hamburg-Eppendorf We implemented this initial

study phase over a 6-month period in order to test the

standard operating procedures and to evaluate the

feasibil-ity of CALM in our setting Patient recruitment followed

the procedure outlined for the CALM RCT, except (a)

pa-tients were not screened for distress (DT/PHQ-9) to be

considered eligible for the study and (b) there was no

randomization: all participants were assigned to the

inter-vention condition Our pilot phase included an evaluation

of each CALM therapy session and a semi-structured

interview after completing at least three therapy sessions

The semi-structured interview focused on how

partici-pants experienced or evaluated (a) the overall CALM

ther-apy; (b) each of the four CALM dimensions; (c) the

therapeutic alliance, and (d) the structure and timeframe

of CALM

Description of the experimental (CALM) and control (SPI)

interventions

Managing Cancer and Living Meaningfully (CALM)

Patients in the IG receive the brief, individual,

manua-lized CALM intervention [20, 26] This semi-structured

psychotherapeutic intervention was designed for

pa-tients with advanced cancer and is based on empirical

research results, clinical observations and theoretical

concepts of supportive-expressive, existential, and

psy-chodynamic therapy as well as stress- and

problem-solving trainings CALM covers the following four

domains:

(1)Symptom management and communication with

health care providers: Within this domain,

cooperation and improvement of communication

with health care providers, and help regarding

medical decision-making to ensure best care and

control of symptoms are addressed;

(2)Changes in self and relations with close others:

Within this domain, supporting the adjustment of

self-esteem and identity to cancer-related changes,

also in regard to relationships with close others, and

sustaining and providing required care and support

are addressed;

(3)Spirituality, sense of meaning and purpose: Within this

domain, understanding the individual meaning of

suffering and dying, and evaluation of priorities and goals facing an advanced disease are addressed; (4)Preparing for the future, sustaining hope and facing mortality: Within this domain, acknowledgment of anticipatory fears, balancing life and death, planning advanced treatment, and preparing the process of dying are addressed

In each CALM session, the patient decides which one of these domains and to what extent each domain

is covered depending on their current concerns and supportive care needs During a period of 6 months, patients in the IG receive up to eight sessions of indi-vidual therapy, each lasting 50 min

Non-manualized supportive psycho-oncological intervention (SPI)

Patients in the CG receive a non-manualized supportive psycho-oncological intervention, which is regularly con-ducted by psychotherapists at both study centers, the Outpatient Cancer Counseling Center at the Section of Psychosocial Oncology, Department of Medical Psych-ology and Medical SociPsych-ology, University Medical Center Leipzig, and the Outpatient Clinic for Psycho-oncology

at the Department of Medical Psychology, University Medical Center Hamburg-Eppendorf The therapeutic approach is based on an integrative approach consisting

of psycho-oncological counseling, information, crisis intervention as well as supportive individual therapy As

IG patients, CG patients receive up to eight sessions of individual therapy during a period of 6 months, each session lasting 50 min

Participants and procedure

We are recruiting patients at both study centers in Hamburg and Leipzig as well as in local university cancer care units and external cancer care facilities Pa-tients with advanced cancer are contacted by a study re-search assistant and assessed for eligibility by using the depression module of the Patient Health Questionnaire (PHQ-9) [27–29] and the Distress Thermometer (DT) [30]

as screening tools Patients fulfilling the inclusion criteria are subsequently invited to a face-to-face interview with the research assistant to receive comprehensive information about our RCT Further inclusion and exclusion criteria are evaluated The study research assistant conducts the Short Orientation Memory Concentration test (SOMC) [31, 32] and the depression section of the Structured Clinical Inter-view for DSM-IV (SCID-I) [33] to evaluate whether pa-tients meet the criteria for a major depressive disorder If patients meet all inclusion criteria and are willing to participate, they are randomized (single-blinded) in ei-ther the intervention or the control group At the end

of the face-to-face interview patients receive the

baseline questionnaire with a prepaid envelope and are

asked to return it within 2 weeks

All patients provide written informed consent prior to

participation Principles of good research practice are

strictly adhered to in this project including data and

pa-tients’ privacy protection Patients can withdraw their

in-formed consent at all times without having to fear any

disadvantage in their medical or psychological treatment In

case patients decide not to participate in the study or to

withdraw informed consent, reasons as well as basic

demo-graphic and medical characteristics (age, sex, diagnosis, date

of diagnosis, educational background) are documented on a

voluntary basis These data will be used to conduct

non-responder analyses and identify a potential sample bias

Eligibility for study participation

Study inclusion criteria

We include patients with (a) a malignant solid tumor who

have (b) tumor stages of III or IV in accordance to the

UICC classification, including advanced disease in case of

sarcoma, melanoma and endocrine tumors, which implies

average life expectancies between 12 and 18 months

Patients who are included in the study (c) are at least

18 years old, (d) speak German fluently, (e) score greater

than or equal to nine on the PHQ-9 or/and greater than

or equal to five on the Distress Thermometer (DT) It is

further necessary that (f) there is no evidence of severe

cog-nitive impairments in the patient’s records or indicated by

his or her physician or oncologist, as this would interfere

with the practical performance of the psychotherapeutic

in-terventions (CALM and SPI)

Study exclusion criteria

During the face-to-face interview the study research

assistant evaluates the following exclusion criteria: (a)

deficits in communication, (b) lack of willingness or

in-ability to attend all of the necessary therapy sessions

and (c) acute suicidality (concrete suicidal thoughts

and/or plans, in which case psychiatric care is provided

immediately) Patients who (d) score less than 20 points

on the Short Orientation-Memory-Concentration test

(SOMC) or (e) show a level of less than 70 on the

Kar-nofsky index are excluded, because life expectancy in that

case is expected to be less than 6 months [34, 35] Patients

will be further excluded from the study in case they

re-ceive parallel psychotherapy Previous experiences with

psychotherapy as well as concurrent

psychopharmaco-logical treatment are documented but are no reasons

to be excluded from study participation

Later study exclusion criteria

Patients will be excluded from the study, if exclusion

criteria occur during the intervention (e.g cognitive

im-pairments) or if patients show signs of acute suicidality

(concrete thoughts and/or plans to commit suicide), in which case psychiatric care will be provided immedi-ately At the point of exclusion, study results up to this date and reasons for exclusion will be documented These data will be further analyzed in the drop-out analysis

Randomization procedure

Study participants are randomly assigned to receive either CALM or SPI The random allocation sequence (randomization list) was generated by the Institute of Medical Biometry and Epidemiology at the University Medical Center Hamburg-Eppendorf Randomization

is stratified according to sex After a patient gives writ-ten informed consent for study participation, a study research assistant reports the patients’ initials, date of birth and sex to a blinded research assistant at the Uni-versity Medical Center in Leipzig The research assistant includes the patient in the randomization list and informs the research assistant about treatment allocation (CALM or SPI) No CALM study member and research assistant has access to the randomization list The patient is not in-formed about their treatment condition

Assessment Baseline assessment

The baseline questionnaire (t0) is handed to the patient

by the research assistant at the end of the face-to-face interview and includes all primary and secondary out-come measures, except for the PHQ-9 depression inven-tory and the Distress Thermometer, which have been used as screening instruments to assess eligibility prior

to the interview, and the GAD-7 anxiety inventory (Table 1)

Follow-up assessments

Two follow-up assessments are realized at three (t1) and

6 months (t2) following the baseline assessment The follow-up assessments ideally correspond with the com-pletion of the third or fourth and the sixth to eighth CALM therapy session Participants receive the study questionnaires with a prepaid envelope and are asked to return them within 2 weeks Those have not returned the study questionnaires within 2 weeks receive a re-minder If patients do not reply within one week after the reminder, the study research assistant will contact them by phone The follow-up measures include the as-sessment of changes in demographics as well as medical and treatment-related events (e g new diagnoses or complications, hospitalization in the past 3 months, whether patient signed a living-will in the past 3 months) and other significant life events

Evaluation of individual therapy sessions

Following each CALM or SPI therapy session, patients and

therapists complete the Clinical Evaluation Questionnaire

[36] This questionnaire measures to what extent patients

perceived their therapy session as helpful, and to what

ex-tent therapists felt they were supportive to the relevant

aspects

Both treatment conditions (IG and CG) end after

6 months and a maximum of eight sessions Therefore,

the last outcome assessment of the study takes place

after 6 months and a maximum of eight sessions If

there is a further need for psychosocial support we offer

participants the possibility to receive further treatment

after study completion – either by their study therapist

or a newly assigned one, according to capacity

Quality standards and therapists training

The CALM treatment manual

We translated and adapted the CALM treatment manual

[37] into the German language

Therapist qualifications

Our study therapists are certified psychologists with

additional psycho-oncological and/or psychotherapeutic

training All study therapists are pair-randomized to the

treatment conditions (IG and CG) to minimize a pos-sible bias

CALM training

CALM therapists receive a comprehensive CALM training

at each study center in Hamburg or Leipzig Therapists randomized to the control condition do not receive any additional training

Supervision

To ensure the quality of the therapy under both treat-ment conditions, both CALM and SPI therapists receive regular supervision by experienced supervisors in separ-ate groups The supervisor of the IG has received the same comprehensive CALM training

Tape recording

Every therapy session in both treatment conditions is audio taped Our research team will analyze audio re-cordings of randomly selected therapy sessions to evalu-ate treatments regarding process quality

Main study hypotheses

We hypothesize that patients in the CALM intervention will show a significantly lower level of depression 6 months

Table 1 Study measures

Screening/face-to-face interview

(baseline) (3 months

follow-up)

(6 months follow-up)

Short Orientation-Memory-Concentration test (SOMC) X

Structured Clinical Interview for DSM Disorders:

Major Depressive Disorder Module

Functional Assessment of Chronic Illness Therapy-Spiritual

Well-Being Scale

The Experience in Close Relationships Inventory

Modified Short Term Version

after baseline compared to patients in the control group

(SPI) We further hypothesize a significant reduction in

anxiety and fatigue as well as significant improvements in

psychological and spiritual well-being, meaning and

post-traumatic growth in the CALM intervention compared to

SPI 6 months after baseline

Measures

Table 1 shows all study measures included in our CALM

RCT We are collecting demographic information (e g age,

sex, marital status, education, occupational situation)

through a standardized questionnaire as well as medical

and treatment-related variables (e g cancer diagnosis, date

of diagnosis, past and current medical treatments) through

medical charts

The Short Orientation-Memory-Concentration test

(SOMC) [31, 32] is a validated culture-fair instrument

for assessing orientation, memory and concentration

The SOMC scores range from 0 to 28 Scores less than

20 indicate cognitive impairments

The Structured Clinical Interview for DSM-IV (SCID-I)

[33] is a valid structured interview and the gold standard

for assessing DSM-IV Axis I disorders We use the 15

items representing the DSM criteria for a major depressive

disorder in the face-to-face interview to screen whether

patients meet the criteria for a major depressive disorder

The interviewer evaluates to what extent a patient’s answers

meet the depression criteria from one (criterion not met) to

three (criterion is fully met) To diagnose a major

depres-sive episode at least five out of nine symptoms need to be

scored with 3, one being item 1 or 2

The German version of the Distress Thermometer (DT)

[30] is a valid and reliable self-report instrument for

screening psychological distress in cancer patients The

single-item visual analogue scale ranges from 0 (no

dis-tress) to 10 (extreme disdis-tress) to quantify the global level

of distress and is accompanied by a standardized

symp-tom checklist In our RCT, only the single-item visual

analogue scale is used Scores equal to or higher than

five indicate significant psychological distress

The Depression module of the Patient Health

Question-naire (PHQ-9) [27–29] is a valid self-report screening

in-strument for depression It includes nine items, which

reflect the DSM-IV criteria for major depression Items are

scored on a four-point Likert scale from 0 (not at all) to 3

(nearly every day) with a total score ranging from 0 to 27

Scores up to four indicate absence of depression, scores

from five to nine indicate mild depression, scores from 10

to 15 indicate moderate depression, and scores higher than

15 indicate severe levels of depression [38] The German

adaptation of the instrument shows high internal

consistency with Cronbach’s α = 89 [39]

The Beck Depression-Inventory II (BDI-II) [40] is a

valid self-report questionnaire evaluating the severity of

depression The measure consists of 21 items, which re-flect the DSM-IV symptom criteria for a major depres-sive disorder Items are scored on a four-point Likert-scale rated from 0 (I don’t feel particularly guilty) to 3 (I feel guilty all of the time) with a total score ranging from 0 to

63 Scores up to 13 indicate none or minimal depression, scores from 14 to 19 indicate mild depression, scores from

20 to 28 indicate moderate depression and scores higher than 29 indicate severe depression The German BDI-II version [40] shows high internal consistency with Cronbach’s α ≥.84 for various samples [41]

The Generalized Anxiety Disorder Questionnaire (GAD-7) [42, 43] is a brief self-report questionnaire assessing generalized anxiety disorder It includes seven items, which reflect the DSM-IV symptom criteria for generalized anxiety disorder Items are scored on a four-point Likert scale ranging from 0 (not at all) to 3 (nearly every day) with a total score ranging from 0 to 21 Scores

up to 4 indicate absence of anxiety, scores from 5 to 9 indi-cate mild anxiety, scores from 10 to 15 indiindi-cate moderate anxiety, and scores higher than15 indicate severe levels of anxiety The German adaptation of the instrument shows high internal consistency with Cronbach’s α = 89

The German version of the Demoralization Scale (DS) [44, 45] is a validated self-report instrument measuring demoralization [46] The scale includes 24 items repre-senting four subscales: loss of meaning and purpose, dysphoria, disheartenment and sense of failure Items are scored on a five-point Likert scale ranging from 0 (never) to 4 (all the time) with a total score ranging from

0 to 96 Scores less than or equal to 30 indicate low demoralization whereas a score greater than 30 indicate high demoralization The German version shows high internal consistency with Cronbach’s α = 0.84 [45] The Brief Fatigue Inventory (BFI) [47, 48] is a short, validated instrument for assessing the severity of fatigue

in cancer patients After patients stated whether they felt unusually tired or fatigued during the past week, nine items measure experienced fatigue as well as its interfer-ence with certain aspects of patients’ lives within the last

24 h Fatigue is rated on an eleven-point Likert-scale from 0 (no fatigue/does not interfere) to 10 (as bad as you can imagine/completely interferes) The mean BFI score is calculated from the nine items, with 1–4 indicat-ing mild, 5–6 moderate and 7–10 severe fatigue The German version shows high internal consistency with Cronbach’s α = 0.92 [48]

The Memorial Symptom Assessment Scale (MSAS) [49, 50] is a validated self-report instrument assessing the number of physical problems that may occur as a result of cancer or its treatment For our study we use the list of symptoms suggested by Chang et al [50] in their adapted version (Short Form) The

MSAS-SF assesses symptom frequency and resulting distress

only Items are scored on a five-point Likert-scale

ran-ging from 0 (not at all) to 4 (very much) The average

symptom score is calculated The scale shows high

in-ternal consistency with Cronbach’s α = 0.87 We did

not include the four psychological items of the

MSAS-SF in our study because we assess psychological

symp-toms using other validated instruments

The German version of the Functional Assessment of

Chronic Illness Therapy-Spiritual Well-Being Scale

(FACIT-SP) [51] is part of the FACIT measurement

sys-tem The self-report instrument measures in what way

spirituality and religion contribute to the quality of life

of cancer patients on the two subscales meaning/peace

and faith Items are scored on a five-point Likert-scale

from 0 (not at all) to 4 (very much) with a total score

ranging from 0 to 48, high scores indicating higher

spir-itual well-being Subscales and the sum score show high

internal consistency with Cronbach’s α = 80

The Death and Dying Distress Scale (DADDS) [52, 53]

is a self-report instrument assessing specific concerns of

advanced cancer patients concerning insecurity about

ones end of life, being a burden to others, as well as lost

time and opportunities The German adaptation includes

nine instead of 15 items Additionally, the Likert-scale

was changed from a six-point to a five-point Likert-scale

with mild and moderate distress put together to one

label Items can be scored from 0 (no distress) to 4 (very

much distress), resulting in a sum score from 0 to 36, a

higher score indicating higher distress

The German version of the Posttraumatic Growth

In-ventory (PTGI)[54, 55] is a self-report instrument

asses-sing personal posttraumatic growth after a traumatic

event It consists of 21 items representing four subscales:

new possibilities, relating to others, appreciation of life

and spiritual change Patients are asked if their life

chan-ged because of their cancer diagnosis Items are scored

on a three-point Likert-scale ranging from 0 (not at all)

to 2 (very much) with a total score ranging from 0 to 42,

a high score indicating high posttraumatic growth The

German version shows high internal consistency with

Cronbach’s α = 0.92 [55]

The Experiences in Close Relationships Scale

(ECR-M16)[56, 57] is a self-report instrument assessing

pa-tients’ experiences in close romantic as well as

non-romantic relationships on two subscales anxiety and

avoidance It is a shorter version of the ECR-36 [56]

in-cluding 16 items due to usage in groups of highly

dis-tressed patients Items are scored on a seven-point

Likert-scale ranging from 1 (disagree) to 7 (agree) with

a total score ranging from 16 to 56 on each subscale

Higher scores on one or both subscales indicate high

attachment insecurity Both subscales show high

in-ternal consistency with Cronbach’s α = 0.91 (anxiety)

andα = 0.88 (avoidance) [57]

The Quality of Life at the End of Life Cancer (QUAL-EC) [58] is a self-report instrument assessing quality of life in patients at the end of their lives regarding their perception

of a good death The instrument includes five subscales: symptom control, relationship with health care provider, preparation for end of life and life completion It includes

17 items, the first three items measuring symptom control and referring to three physical or emotional symptoms the patient has to name at the beginning We used items 4–17 measuring the remaining three subscales Items are scored

on a five-point Likert-scale ranging from 1 (not at all) to 5 (completely) with a total score ranging from 14 to 70, high scores indicating high quality of life The instrument shows high internal consistency with Cronbach’s α = 0.83

The Couple Communication Scale (CCS) [59] is an online-measure for assessing communication, conflict solution and relationship satisfaction in romantic rela-tionships and was developed as a part of the ENRICH/ PREPARE program [60] The scale is part of the Couple Checkup Scale which includes 32 items covering – de-pending on relationship status (dating, engaged, mar-ried) – different aspects of romantic relationships that were found to be important for a happy marriage In ac-cordance with G Rodin and colleagues we only used the ten items depicting communication in romantic relation-ships in our study Items can be scored from 1 (strongly disagree) to 5 (strongly agree)

The Clinical Evaluation Questionnaire [36] is a self-report seven-item questionnaire assessing the extent to which a therapeutic session was perceived as helpful for patients on such dimensions as being able to discuss their concerns about cancer and their treatment options and to clarify their values The questionnaire is answered

on a five-point Likert scale, ranging from 0 (not at all) to

4 (very much) Higher values indicate a higher degree of perceived benefit If a certain aspect is not relevant, items can be rated as not applicable

In case there was no German adaptation of the instru-ment available, we used state-of-the-art forward- back-translation by two independent research assistants

Statistical methods Power calculation

To determine the sample size in a design in which two groups are compared at follow-up, controlling for baseline scores, we used the formula n = [2(ZA+ ZB)2(1− r2

)/d2] + 1 suggested by Borm [61] In a longitudinal study by Rodin et

al [25], a correlation of 72 (based on n=137)between de-pression scores (BDI-II) at baseline and 6 months, as well

as a SD of 7.4 at baseline were observed Therefore, we used r = 70 and SD = 7.4 as our estimates The goal of this RCT is to detect an effect size of Cohen’s d = 405 (d = (X1

− X2)/SD) [62] in depression scores between both groups

(i.e (X1− X2) = d*SD = 405*7.4 = 3) Considering these

fac-tors, a minimum of 50 participants is required at t2

The number of participants that need to be recruited

per group at baseline is calculated by taking into account

the effects of loss to follow-up and non-compliance

using the formula n-b= ne(1/p) (1/c2[63, 64] Based on

trial completion rates and compliance rates at 6 months

observed in similar trials, we estimate a completion rate

of 60 % (i.e loss to follow-up rate of 40 %) and an 80 %

compliance rate [65, 66] Therefore, we need to recruit

131 participants per group, or 262 total participants at

baseline Recruitment is equally divided between Hamburg

and Leipzig, resulting in a number of 66 IG patients and 66

CG patients for Hamburg and 65 patients in each group for

Leipzig The adjustment for non-compliance is conservative

as it assumes that non-compliant experimental participants

will respond as though they were control participants

Statistical analysis

For the final analyses we will use an intention-to-treat

approach (ITT) and compare patients in the assigned

treatment groups Main analyses to evaluate efficacy

based on primary (depression) and secondary outcomes

at 6 months follow-up (primary endpoint) will be

per-formed using analysis of covariance (ANCOVA) In case

of missing outcome data at the primary endpoint, we

use the last observation carried forward (LOCF) method

Controlling for baseline test scores as well as demographic

and disease-related characteristics, we hypothesize that the

mean depression score in the IG will be lower than the one

in the CG Other analyses will include a mixed model

ap-proaches (to examine changes over time), regression

ana-lyses (controlling for additional factors), and exploratory

analyses (of treatment effect modifiers)

Discussion

In the last decades, existential and psychosocial needs of

patients in palliative care became increasingly the focus

of attention in clinical practice and research The new

World Health Organization (WHO) palliative care

reso-lution ‘Strengthening of palliative care as a component

of integrated treatment within the continuum of care’

just recently made clear that palliative care is aimed to

be integrated as an essential component of health care

systems worldwide [67] In this resolution the WHO

Executive Board explicitly refers to psychosocial and

spiritual problems and their treatment Despite the

pronounced necessity for better psychosocial care in

palliative treatment, recent studies investigating the

ef-fectiveness of psycho-oncological interventions are

mostly including patients in earlier stages of the cancer

disease Most RCTs have small sample sizes and

com-pare one active intervention against an inactive control

group, no treatment, or care as usual [17]

Our CALM RCT adapted to German cancer care set-tings addresses the urgent need for developing, optimiz-ing and evaluating manualized psycho-oncologic interventions for advanced cancer patients To ensure optimal treatment for advanced patients’ specific existen-tial and psychosocial strains it aims to close the gap of treatment options by implementing a short-term, indi-vidual and meaning-based intervention

CALM is already under examination in a RCT in Toronto, Canada, by the research group of Prof G Rodin who developed CALM Our RCT is conducted in close cooperation with the Canadian research group, which ensures research quality and helps us to be pre-pared for possible risks and obstacles during the trial Currently, studies examining CALM are also conducted

in Italy and the United Kingdom, which will lead to a growing international application of the intervention as

a psychological dimension of early palliative care As one

of the few psycho-oncological interventions dealing with these issues, our study will contribute important statis-tical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients

Abbreviations

CALM: Managing Cancer and Living Meaningfully; CAU: Care as usual; CG: Control group; DT: Distress thermometer; IG: Intervention group; ITT: Intention-to-treat; LOCF: Last observation carried forward; RCT: Randomized controlled trial; SPI: Non-manualized supportive psycho-oncological intervention.

Competing interests The authors declare that they have no competing interests.

Authors ’ contributions All authors contributed to the design of the study AM and MH are the principal investigators of the study in Leipzig and Hamburg AM, FSK, CR, KO were together with CL, SH and GR responsible for conceptualizing the German CALM trial and grant proposal AM, KS, RP and DE drafted the paper, which was modified and supplemented by all other authors KW is responsible for the standardized randomization procedure FSK, KS, DE, KO,

CR, FL and RP are involved in recruiting participants while KS and DE take care of the logistics of the study and data collection All authors read and approved the final manuscript.

Acknowledgements This research is funded by the German Cancer Aid (Grant numbers: 109967, 110746).

Author details

1 Department and Outpatient Clinic of Medical Psychology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.

2 Department of Medical Psychology and Medical Sociology, Section of Psychosocial Oncology, University Medical Center Leipzig,

Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany 3 Department of Oncology, Hematology and Bone Marrow Transplantation with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.4Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.5University Medical Center Leipzig, University Cancer Center Leipzig (UCCL), Liebigstrasse 20, Leipzig 04103, Germany 6 Department of Supportive Care, 16-724, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada.

Received: 11 June 2015 Accepted: 30 July 2015

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